Safety evaluation of the food enzyme β‐fructofuranosidase from the non‐genetically modified Aspergillus sp. strain ATCC 20611

TL;DR

This study evaluates the safety of a food enzyme produced by a non-genetically modified fungus for use in making fructo-oligosaccharides.

Contribution

The novelty lies in the safety assessment of β-fructofuranosidase from Aspergillus sp. ATCC 20611 for food use.

Findings

Genotoxicity tests showed no safety concerns.

The no observed adverse effect level was 920 mg TOS/kg body weight per day.

Risk of allergic reactions is considered low.

Abstract

The food enzyme β‐fructofuranosidase (β‐d‐fructofuranoside fructohydrolase; EC 3.2.1.26) is produced with the non‐genetically modified Aspergillus sp. strain ATCC 20611 by Beghin Meiji. The food enzyme was free from viable cells of the production organism. It is intended to be used in the processing of sugars for the production of fructo‐oligosaccharides (FOS). Since residual amounts of total organic solids of the food enzyme are removed in FOS syrups, dietary exposure was not calculated. The toxicological studies were assessed as supportive evidence. Genotoxicity tests did not indicate a safety concern. The systemic toxicity was assessed by means of a repeated dose 90‐day oral toxicity study in rats. The Panel identified a no observed adverse effect level of 920 mg TOS/kg body weight (bw) per day, the highest dose tested. A search for the homology of the amino acid sequence of the β‐fructofuranosidase to known allergens was made and no match was found. The Panel considered that a risk of allergic reactions upon dietary exposure to the food enzyme cannot be excluded, but that the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns, under the intended conditions of use.

Tables

TABLE 1. Composition of the food enzyme.

Parameters	Unit	Batches
		1	2	3	4 a
β ‐Fructofuranosidase activity	U/g b	16,900,000	12,800,000	14,900,000	13,400,000
Protein	%	28.7	27.8	28.3	25.8
Ash	%	3.5	4.0	3.9	4.2
Water	%	4.7	4.0	3.6	3.8
Total organic solids (TOS) c	%	91.8	92.0	92.5	92.0
Activity/TOS ratio	U/mg TOS	18,410	13,913	16,108	14,565

TABLE 2. Intended uses and recommended use levels of the food enzyme as provided by the applicant. 29

Food manufacturing process a	Raw material (RM)	Recommended use level (mg TOS/kg RM) b
Processing of sugars
Production of oligosaccharides	Sucrose	1.691 c	Immobilised form
		13.995 d	Non‐immobilised form

TABLE 3. Qualitative evaluation of the influence of uncertainties on the dietary exposure estimate.

Sources of uncertainties	Direction of impact
Model assumptions and factors
Exclusion of one process from the exposure estimation: – production of oligosaccharides	–

Full text

INTRODUCTION

1

Article 3 of the Regulation (EC) No 1332/20081 provides definition for ‘food enzyme’ and ‘food enzyme preparation’.

‘Food enzyme’ means a product obtained from plants, animals or micro‐organisms or products thereof including a product obtained by a fermentation process using micro‐organisms: (i) containing one or more enzymes capable of catalysing a specific biochemical reaction; and (ii) added to food for a technological purpose at any stage of the manufacturing, processing, preparation, treatment, packaging, transport or storage of foods.

‘Food enzyme preparation’ means a formulation consisting of one or more food enzymes in which substances such as food additives and/or other food ingredients are incorporated to facilitate their storage, sale, standardisation, dilution or dissolution.

Before January 2009, food enzymes other than those used as food additives were not regulated or were regulated as processing aids under the legislation of the Member States. On 20 January 2009, Regulation (EC) No 1332/2008 on food enzymes came into force. This Regulation applies to enzymes that are added to food to perform a technological function in the manufacture, processing, preparation, treatment, packaging, transport or storage of such food, including enzymes used as processing aids. Regulation (EC) No 1331/20082 established the European Union (EU) procedures for the safety assessment and the authorisation procedure of food additives, food enzymes and food flavourings. The use of a food enzyme shall be authorised only if it is demonstrated that:

• it does not pose a safety concern to the health of the consumer at the level of use proposed;
• there is a reasonable technological need;
• its use does not mislead the consumer.

All food enzymes currently on the EU market and intended to remain on that market, as well as all new food enzymes, shall be subjected to a safety evaluation by the European Food Safety Authority (EFSA) and approval via an EU Community list.

The ‘Guidance on submission of a dossier on food enzymes for safety evaluation’ (EFSA, 2009a) lays down the administrative, technical and toxicological data required.

Background and Terms of Reference as provided by the requestor

1.1

Background as provided by the European Commission

1.1.1

Only food enzymes included in the European Union (EU) Community list may be placed on the market as such and used in foods, in accordance with the specifications and conditions of use provided for in Article 7(2) of Regulation (4EC) No 1332/20081 on food enzymes.

Five applications have been introduced by the Association of Manufacturers and Formulators of Enzyme Products (AMFEP) for the authorisation of the food enzyme Bacillolysin from Bacillus amyloliquefaciens and the companies ‘Danisco US Inc.’ for the authorisation of the food enzymes Alpha‐amylase from a genetically modified strain of Bacillus licheniformis (DP‐Dzb44), Beta‐galactosidase from a genetically modified strain of Bacillus subtilis (DP‐Ezg29) and Endo‐1,4‐beta‐xylanase from a genetically modified strain of Bacillus subtilis (DP‐Ezd31), and ‘Beghin Meiji’ for the authorisation of the food enzyme Beta‐Fructofuranosidase from Aspergillus fijiensis (Strain ATCC® 20611™).

Following the requirements of Article 12.1 of Regulation (EC) No 234/2011^3^ implementing Regulation (EC) No 1331/2008,^2^ the Commission has verified that the five applications fall within the scope of the food enzyme Regulation and contain all the elements required under Chapter II of that Regulation.

Terms of Reference

1.1.2

The European Commission requests the European Food Safety Authority to carry out the safety assessments on the food enzymes Alpha‐amylase from a genetically modified strain of Bacillus licheniformis (DP‐Dzb44), Bacillolysin from Bacillus amyloliquefaciens, Beta‐galactosidase from a genetically modified strain of Bacillus subtilis (DP‐Ezg29), Endo‐1,4‐beta‐xylanase from a genetically modified strain of Bacillus subtilis (DP‐Ezd31) and Beta‐Fructofuranosidase from Aspergillus fijiensis (Strain ATCC® 20611™) in accordance with Article 17.3 of Regulation (EC) No 1332/2008^1^ on food enzymes.

Interpretation of the Terms of Reference

1.2

The present scientific opinion addresses the European Commission's request to carry out the safety assessment of the food enzyme β‐fructofuranosidase from Aspergillus fijiensis (strain ATCC® 20611™) submitted by Beghin Meiji.

Recent data did not allow to identify the species of the production microorganism as Aspergillus fijiensis (see Section 3.1). Therefore, the name Aspergillus sp. will be used in this opinion.

DATA AND METHODOLOGIES

2

Data

2.1

The applicant has submitted a dossier in support of the application for authorisation of the food enzyme β‐fructofuranosidase from Aspergillus fijiensis (Strain ATCC® 20611™).

Additional information was requested from the applicant during the assessment process on 28 February 2023 and received on 12 November 2023 (see ‘Documentation provided to EFSA’).

Methodologies

2.2

The assessment was conducted in line with the principles described in the EFSA ‘Guidance on transparency in the scientific aspects of risk assessment’ (EFSA, 2009a) and following the relevant guidance documents of the EFSA Scientific Committee.

The ‘Guidance on the submission of a dossier on food enzymes for safety evaluation’ (EFSA, 2009b) as well as the ‘Statement on characterisation of microorganisms used for the production of food enzymes’ (EFSA CEP Panel, 2019) have been followed for the evaluation of the application. Additional information was requested in accordance with the updated ‘Scientific Guidance for the submission of dossiers on food enzymes’ (EFSA CEP Panel, 2021) and the guidance on the ‘Food manufacturing processes and technical data used in the exposure assessment of food enzymes’ (EFSA CEP Panel, 2023).

ASSESSMENT

3

IUBMB nomenclatureβ‐FructofuranosidaseSystematic nameβ‐d‐Fructofuranoside fructohydrolaseSynonymsInvertase; saccharase; glucosucrase; β‐fructosidaseIUBMB NoEC 3.2.1.26CAS No9001‐57‐4EINECS No232‐615‐7

β‐Fructofuranosidases catalyse the hydrolysis of the glycosidic linkage of sucrose, releasing fructose and glucose. They may also catalyse fructotransferase reactions. The food enzyme under assessment is intended to be used in the processing of sugars for the production of fructo‐oligosaccharides (FOS), as defined in the EFSA guidance (EFSA CEP Panel, 2023).

Source of the food enzyme

3.1

The β‐fructofuranosidase is produced with the filamentous fungus strain ATCC 20611 which is deposited at the American Type Culture Collection (ATCC, US) as Aspergillus fijiensis. The data provided do not allow an unambiguous distinction among Aspergillus species. Therefore, the strain is reported here as Aspergillus sp.

Production of the food enzyme

3.2

The food enzyme is manufactured according to the Food Hygiene Regulation (EC) No 852/20043, with food safety procedures based on Hazard Analysis and Critical Control Points, and in accordance with Good Manufacturing Practice.4

The production strain is grown as a pure culture using a typical industrial medium in a ■■■■■ fermentation system with conventional process controls in place. After completion of the fermentation, the solid biomass is removed from the fermentation broth by filtration. The filtrate containing the enzyme is then further purified and concentrated, including an ultrafiltration step in which enzyme protein is retained, while most of the low molecular mass material passes the filtration membrane and is discarded. Finally, the food enzyme was spray‐dried prior to analysis.5 The applicant provided information on the identity of the substances used to control the fermentation and in the subsequent downstream processing of the food enzyme.6

The food enzyme can also be used in an immobilised form. Immobilisation is achieved by adsorption of the food enzyme onto a support resin based on a ■■■■■. The resin beads with the adsorbed food enzyme are then washed and dried.6 7

The Panel considered that sufficient information has been provided on the manufacturing process and the quality assurance system implemented by the applicant to exclude issues of concern.

Characteristics of the food enzyme

3.3

Properties of the food enzyme

3.3.1

The β‐fructofuranosidase is a single polypeptide chain of ■■■■■.8 The molecular mass of the mature protein, calculated from the amino acid sequence, is ■■■■■.9 The food enzyme was analysed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis. A consistent protein pattern was observed across all batches. The gel showed a major protein band of about ■■■■■ that can be consistent with a glycosylated form of the enzyme.10

No other enzyme activities were reported.

The applicant's in‐house determination of β‐fructofuranosidase activity is based on its fructosyl transferase activity using ■■■■■ as a substrate (reaction conditions: ■■■■■). The enzyme activity is determined by measuring the generation of the ■■■■■ by high‐performance liquid chromatography (HPLC). The enzyme activity is expressed in Unit (U)/g. One unit of fructosyl transferase activity is defined as the amount of the enzyme that produces 1 μmol of ■■■■■ per hour under the conditions of the assay.11

The food enzyme has a temperature optimum between 50°C and 60°C (■■■■■) and a pH optimum between 5.0 and 6.0 (■■■■■). Thermostability was tested by pre‐incubation of the food enzyme for 30 min at different temperatures (■■■■■). Enzyme activity decreased above 30°C showing around 50% residual activity at 70°C.12

Chemical parameters

3.3.2

Data on the chemical parameters of the food enzyme were provided for four food enzyme batches intended for commercialisation among which batch 4 was used for the toxicological tests (Table 1).13 The mean total organic solids (TOS) of the four batches was 92.1% and the mean enzyme activity/TOS ratio was 15,749 U/mg TOS. The applicant provided also data for three food enzyme batches intended for commercialisation recently produced and they have similar chemical composition as those reported in Table 1.14

Purity

3.3.3

The lead content in all batches was below 5 mg/kg15 which complies with the specification for lead as laid down in the general specifications for enzymes used in food processing (FAO/WHO, 2006). In addition, arsenic and mercury concentrations were below the limits of quantification (LoQs) of the employed methods.16 For cadmium, the average concentration determined in all batches was 0.03 mg/kg.17 ^,^ 18 The Panel considered this concentration as not of concern.

The food enzyme complies with the criteria for total coliforms, Escherichia coli and Salmonella, as laid down in the general specifications for enzymes used in food processing (FAO/WHO, 2006).19 No antimicrobial activity was detected in any of the tested batches.20

Strains of Aspergillus species, in common with most filamentous fungi, have the capacity to produce a range of secondary metabolites (Frisvad et al., 2018). The presence of ochratoxin A, aflatoxins (B1, B2, G1, G2) and sterigmatocystin was examined in all food enzyme batches and were below the limits of quantification of the applied analytical methods.21 ^,^ 22 Adverse effects caused by the possible presence of other secondary metabolites is addressed by the toxicological examination of the food enzyme.

The Panel considered that the information provided on the purity of the food enzyme is sufficient.

Viable cells of the production strain

3.3.4

The absence of viable cells of the production strain in the food enzyme was demonstrated in three independent batches analysed in triplicate. ■■■■■ No colonies of the production strain were detected. A positive control was included.

Toxicological data

3.4

In line with the guidance available at the time of submission (EFSA CEF Panel, 2009), the applicant submitted a battery of toxicological tests. Following the current guidance (EFSA CEP Panel, 2021), the Panel considers that a toxicological testing is not necessary as the food enzyme–TOS are removed (> 99%) in the final foods (see Section 3.5). The toxicological tests (including a bacterial reverse mutation test (Ames test), an in vitro mammalian cell micronucleus test and a repeated dose 90‐day oral toxicity study in rats) were assessed and reported as supporting evidence.

The batch 4 (Table 1) used in these studies is one of the batches intended for commercialisation and is considered suitable as a test item.

Genotoxicity

3.4.1

Bacterial reverse mutation test

3.4.1.1

A bacterial reverse mutation test (Ames test) was performed according to the Organisation for Economic Co‐operation and Development (OECD) Test Guideline 471 (OECD, 1997) and following Good Laboratory Practice (GLP).23 Four strains of Salmonella Typhimurium (TA98, TA100, TA1535 and TA1537) and Escherichia coli WP2uvrA were used with or without metabolic activation (S9‐mix), applying the pre‐incubation method.

Based on the results of a pre‐experiment, two main experiments were carried out in triplicate, using five concentrations of the food enzyme of 288, 575, 1150, 2300 and 4600 μg TOS/plate.

No cytotoxicity was observed at any concentration of the test substance. Upon treatment with the food enzyme there was no biologically relevant increase in the number of revertant colonies above the control values, in any strain tested, with or without S9‐mix.

The study was considered reliable without restrictions and the results of high relevance.

The Panel concluded that the food enzyme β‐fructofuranosidase did not induce gene mutations under the test conditions applied in this study.

In vitro mammalian cell micronucleus test

3.4.1.2

The in vitro mammalian cell micronucleus test was carried out according to OECD Test Guideline 487 (OECD, 2010) and following GLP.24 An experiment was performed with duplicate cultures of mouse lymphoma cells. The cell cultures were treated with the food enzyme with or without metabolic activation (S9‐mix).

Based on the results from the dose‐range finding test, cells were exposed to the food enzyme in a short‐term treatment (3‐h exposure and 21‐h recovery period) and scored for the frequency of micronucleated cells at four concentrations of 1840, 2760, 3680 and 4600 μg TOS/mL with S9‐mix, and at five concentrations of 2300, 2760, 3220, 3680 and 4140 μg TOS/mL without S9‐mix. In the long‐term treatment (24‐h exposure without recovery period), cells were exposed to the food enzyme and scored for micronucleated cells at five concentrations of 460, 920, 1380, 1840 and 2300 μg TOS/mL without S9‐mix.

Cytotoxicity was observed at the highest concentrations tested in the absence of S9‐mix (68% and 88% in the short‐term and in the long‐term treatment, respectively). The frequency of micronucleated cells was not statistically significantly different to the negative controls at all concentrations tested in any of the three treatments.

The study was considered reliable without restrictions and the results of high relevance.

The Panel concluded that the food enzyme β‐fructofuranosidase did not induce an increase in the frequency of micronucleated cells under the test conditions applied in this study.

Repeated dose 90‐day oral toxicity study in rodents

3.4.1.3

The repeated dose 90‐day oral toxicity study was performed under GLP and in accordance with OECD Test Guideline 408 (OECD, 1998).25

Groups of 10 male and 10 female Sprague–Dawley (Crl:CD(SD)) rats received the food enzyme by gavage in doses of 92, 276 or 920 mg TOS/kg body weight (bw) per day. Controls received the vehicle (water for injection).

Haematological investigations revealed a statistically significant increase in the percentage of eosinophils (Eos) in high‐dose females (+40%) and in the platelet count (Plt) in low‐dose females (+14%). The Panel considered the changes as not toxicologically relevant, as they were only observed in one sex (both parameters), there was no dose–response relationship (Plt) and there were no changes in other relevant parameters (for Eos in other white blood cell populations; for Plt in other coagulation parameters).

Clinical chemistry investigations revealed a statistically significant increase in chloride concentration in low‐dose males (+2%), a decrease in total protein in low‐ and mid‐dose males (−3%, −5%) and a decrease in aspartate transaminase (AST) activity in mid‐dose females (−36%). The Panel considered the changes as not toxicologically relevant, as they were only observed in one sex (all parameters), there was no dose–response relationship (all parameters) and the changes were small (all parameters).

The urinalysis revealed a statistically significant increase in the excretion of sodium in low‐ and mid‐dose females (+57%, +71%), of potassium in low‐ and mid‐dose females (+44%, +56%) in chloride in mid‐dose females (+55%), and a decrease in water consumption in low‐dose females (−16%). The Panel considered the changes as not toxicologically relevant, as they were only observed in one sex (all parameters), there was no dose–response relationship (all parameters) and there were no histopathological changes in the kidneys.

Statistically significant changes detected in organ weights were an increase in the absolute seminal vesicle weight in low‐dose males (+16%), and decreases in the relative heart weight in low‐dose males (−10%), the absolute uterus weight in low‐ and mid‐dose females (−16%, −21%) and the relative uterus weight in low‐, mid‐ and high‐dose females (−20%, −25%, −17%). The Panel considered the changes as not toxicologically relevant, as they were only observed in one sex (heart), there was no dose–response relationship (all organs), the change was small (heart) and there were no histopathological changes in the respective organs.

No other statistically significant or toxicologically relevant differences from controls were reported.

The Panel identified a no observed adverse effect level (NOAEL) of 920 mg TOS/kg bw per day, the highest dose tested.

Allergenicity

3.4.1.4

The allergenicity assessment considered only the food enzyme and not additives, carriers or other excipients that may be used in the final formulation.

The potential allergenicity of the β‐fructofuranosidase produced with the Aspergillus fijiensis strain ATCC 20611 was assessed by comparing its amino acid sequence with those of known allergens as described in the EFSA GMO Scientific Opinion (EFSA GMO Panel, 2010). Using higher than 35% identity in a sliding window of 80 amino acids as the criterion, no match was found in the AllergenOnline database.26

No reports on oral or respiratory sensitisation or elicitation reactions of the β‐fructofuranosidase under assessment have been published.27

Immunoglobulin E (IgE) 3.5 reactivity to β‐fructofuranosidase was reported in individuals with respiratory allergy to mould (Horner et al., 2008). Several studies have shown that individuals respiratorily sensitised to a food enzyme are usually able to ingest the corresponding enzyme without acquiring clinical symptoms of food allergy (Armentia et al., 2009; Cullinan et al., 1997; Poulsen, 2004). In other studies, IgE reactivity to β‐fructofuranosidase from tomato has been reported (Foetisch et al., 2003; Kitagawa et al., 2006; Westphal et al., 2003). However, no sequence homology with either of these β‐fructofuranosidases has been identified.

The production strain belongs to the Aspergillus genus, which is known to cause respiratory allergy (Kurup et al., 2000; Shen & Han, 1998; Vermani et al., 2015). Allergic reactions upon dietary exposure have been observed, but are rare (Xing et al., 2022). The biomass is removed during the production process; however, allergenic proteins of the production strain can be released into the culture medium from which the food enzyme is obtained.

■■■■■, a product from soy that may cause allergies or intolerances (listed in the Regulation (EU) No 1169/201128), are used as raw material. During the fermentation process, this product will mostly be degraded by the production strain.

Taken together, concerning the potential allergic reactions due to the production strain and the raw material in the culture medium, the Panel considered that residual amounts of allergenic proteins could be present in the food enzyme. Taking into account the level of dietary exposure (see Section 3.5.2), this would result in minute amounts in the final foods, from which allergic reactions are usually not expected.

In conclusion, the Panel considered that under the intended conditions of use, a risk of allergic reactions upon dietary exposure to this food enzyme cannot be excluded, but that the likelihood is low.

Dietary exposure

3.5

Intended use of the food enzyme

3.5.1

3.5.1.1

The food enzyme is intended to be used in the processing of sugars for the production of FOS at the recommended use levels summarised in Table 2.

TABLE 2: Intended uses and recommended use levels of the food enzyme as provided by the applicant. 29

In the production of oligosaccharides, the non‐immobilised food enzyme is added to sucrose syrup,30 while the immobilised food enzyme is used to treat aqueous sucrose solutions in a continuous process.31 Due to the high concentration of sucrose, the use of the β‐fructofuranosidase will result in formation of FOS by transfructosylation.

When the food enzyme is used in the non‐immobilised form, the downstream processing steps applied, which include filtration, repeated decolorisation with ■■■■■ and fractionation steps, could theoretically remove the food enzyme–TOS from the FOS products.32 Removal of the food enzyme–TOS is expected also when the food enzyme is used in the immobilised form, due to chromatographic and refining processes.33

To substantiate the food enzyme–TOS removal, the applicant measured, as a proxy, the enzymatic activity and the total nitrogen content in three commercial batches of FOS syrups produced with the free form of the enzyme and in three commercial batches of FOS syrups produced with the immobilised form. The results showed a reduction of more than 99% of both β‐fructofuranosidase activity and nitrogen content in the FOS syrups.34 The Panel considered the analytical data provided as sufficient to confirm the absence of food enzyme‐TOS in the FOS syrups.

Dietary exposure estimation

3.5.2

As the Panel accepted the evidence provided as sufficient to conclude that the residual amount of food enzyme–TOS in the FOS syrups is negligible, a dietary exposure was not calculated.

Uncertainty analysis

3.5.3

In accordance with the guidance provided in the EFSA opinion related to uncertainties in dietary exposure assessment (EFSA, 2006), the following sources of uncertainties have been considered and are summarised in Table 3.

The exclusion of one food manufacturing process from the exposure estimation was based on > 99% of TOS removal. This is not expected to impact the overall estimate derived.

Margin of exposure

3.6

Since a dietary exposure was not calculated, a margin of exposure was not derived.

CONCLUSIONS

4

Based on the data provided, the Panel concluded that the food enzyme ß‐fructofuranosidase produced with Aspergillus sp. strain ACTT 20611 does not give rise to safety concerns under the intended conditions of use.

DOCUMENTATION AS PROVIDED TO EFSA

5

Application for the authorisation of ß‐Fructofuranosidase from Aspergillus fijiensis ATCC®20611TM as a Food Enzyme in the European Union. 4 March 2015. Submitted by Beghin Meiji. The dossier was updated on 10 September 2015.

Additional information. November 2023. Submitted by Beghin Meiji.

ABBREVIATIONSbwbody weightCASChemical Abstracts ServiceCEFEFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing AidsCEPEFSA Panel on Food Contact Materials, Enzymes and Processing AidsEINECSEuropean Inventory of Existing Commercial Chemical SubstancesFAOFood and Agricultural Organization of the United NationsGLPGood Laboratory PracticeHPLChigh‐performance liquid chromatographyIUBMBInternational Union of Biochemistry and Molecular BiologyJECFAJoint FAO/WHO Expert Committee on Food AdditiveskDakiloDaltonLoQlimit of quantificationMoEmargin of exposureNOAELNo observed adverse effect levelOECDOrganisation for Economic Cooperation and DevelopmentTOStotal organic solidsWHOWorld Health Organization

REQUESTOR

European Commission

QUESTION NUMBER

EFSA‐Q‐2015‐00840

COPYRIGHT FOR NON‐EFSA CONTENT

EFSA may include images or other content for which it does not hold copyright. In such cases, EFSA indicates the copyright holder and users should seek permission to reproduce the content from the original source.

PANEL MEMBERS

José Manuel Barat Baviera, Claudia Bolognesi, Francesco Catania, Gabriele Gadermaier, Ralf Greiner, Baltasar Mayo, Alicja Mortensen, Yrjö Henrik Roos, Marize LM Solano, Henk Van Loveren, Laurence Vernis, and Holger Zorn.

NOTE

The full opinion will be published in accordance with Article 12 of Regulation (EC) No 1331/2008 once the decision on confidentiality will be received from the European Commission.

LEGAL NOTICE

Relevant information or parts of this scientific output have been blackened in accordance with the confidentiality requests formulated by the applicant pending a decision thereon by EFSA. The full output has been shared with the European Commission, EU Member States (if applicable) and the applicant. The blackening may be subject to review once the decision on the confidentiality requests is adopted by EFSA and in case it rejects some of the confidentiality requests.